MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying PI3K-mediated suppression of HDAC2
نویسندگان
چکیده
Richard Y. Kim, PhD, Jay C. Horvat, PhD, James W. Pinkerton, B Biomed Sci, Malcolm R. Starkey, PhD, Ama T. Essilfie, PhD, Jemma R. Mayall, B Biomed Sci, Prema M. Nair, B Biomed Sci, Nicole G. Hansbro, PhD, Bernadette Jones, BSc, Tatt Jhong Haw, B Biomed Sci, Krishna P. Sunkara, MSc, Thi Hiep Nguyen, MSc, Andrew G. Jarnicki, PhD, Simon Keely, PhD, Joerg Mattes, MD, PhD, Ian M. Adcock, PhD, Paul S. Foster, DSc, Philip M. Hansbro, PhD
منابع مشابه
Passive Smoking Impairs Histone Deacetylase-2 in Children With Severe Asthma
BACKGROUND Parental smoking is known to worsen asthma symptoms in children and to make them refractory to asthma treatment, but the molecular mechanism is unclear. Oxidative stress from tobacco smoke has been reported to impair histone deacetylase-2 (HDAC2) via phosphoinositide-3-kinase (PI3K)/Akt activation and, thus, to reduce corticosteroid sensitivity. The aim of this study was to investiga...
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Glucocorticoids are the most effective antiinflammatory agents for the treatment of chronic inflammatory diseases even though some diseases, such as chronic obstructive pulmonary disease (COPD), are relatively glucocorticoid insensitive. However, the molecular mechanism of this glucocorticoid insensitivity remains uncertain. We show that a defect of glucocorticoid receptor (GR) deacetylation ca...
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Cigarette smoke (CS)-induced lung inflammation involves the reduction of histone deacetylase 2 (HDAC2) abundance, which is associated with steroid resistance in patients with chronic obstructive pulmonary disease and in individuals with severe asthma who smoke cigarettes. However, the molecular mechanism of CS-mediated reduction of HDAC2 is not clearly known. We hypothesized that HDAC2 is phosp...
متن کاملHistone acetylation and deacetylation: importance in inflammatory lung diseases.
Inflammatory lung diseases are characterised by increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-kappa B. Gene expression is regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein, with intrinsic histone acetyltransferase (HAT) activity. Conversely, gene rep...
متن کاملGlucocorticoid receptor β and histone deacetylase 1 and 2 expression in the airways of severe asthma.
RATIONALE Upregulation of glucocorticoid receptor β (GRβ) has been implicated in steroid resistance in severe asthma, although previous studies are conflicting. GRβ has been proposed as a dominant negative isoform of glucocorticoid receptor α (GRα) but it has also been suggested that GRβ can cause steroid resistance via reduced expression of histone deacetylase 2 (HDAC2), a key regulator of ste...
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تاریخ انتشار 2016